Abstract: PO2396
Elevated Donor-Derived Cell-Free DNA (dd-cfDNA) Attributed to Angiotensin II Type 1 Receptor Antibodies (AT1R-Ab) in Renal Re-Transplantation
Session Information
- Clinical and Immunologic Predictors of Post-Transplant Outcomes
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1902 Transplantation: Clinical
Authors
- Coke, Howard H., University of Texas McGovern Medical School, University of Texas John P and Katherine G McGovern Medical School, Houston, Texas, United States
- Van Norman, Matthew, University of Texas McGovern Medical School, University of Texas John P and Katherine G McGovern Medical School, Houston, Texas, United States
- Pai, Akshta, Memorial Hermann Texas Medical Center, Houston, Texas, United States
- De Golovine, Aleksandra, Memorial Hermann Texas Medical Center, Houston, Texas, United States
- Edwards, Angelina, Memorial Hermann Texas Medical Center, Houston, Texas, United States
Introduction
Complications of renal transplants include graft rejection and failure. Noninvasive dd-cfDNA values greater than 1% detect renal allograft injury and rejection, prior to changes in creatinine. Although antibody mediated rejection (AMR) typically involves donor specific antibodies (DSA) to human leukocyte antigens (HLA), non-HLA antibodies may also impact allograft outcomes. This series of re-transplantation patients with graft injury from AT1R-Ab (>10 U/mL) shows improvement in dd-cfDNA levels with initiation of an ARB, Losartan.
Case Description
Case #1: 23 year-old man with history of CKD IV due to hypoplastic kidneys. First transplant living unrelated donor failed due to renal vein thrombosis. Received a 2nd deceased donor transplant (DDRT) with thymoglobulin induction. Combined panel reactive antibodies (cPRA) was 99%, with no DSA. Post-transplant allograft function was excellent with nadir creat of 1.0mg/dL. Non-invasive allograft surveillance was initiated with initial dd-cfDNA (ALLOSURE, CareDx, Brisbane, CA) elevated at 1.8%. Antibody assessment was negative for DSA but positive for AT1R-Ab at 28 U/mL. Losartan was initiated with a sustained decrease in dd-cfDNA to <0.3% and stable creatinine levels.
Case #2: 63 year-old woman with ESRD from hypertension. Prior living donor transplant failed due to chronic allograft nephropathy. Received 2nd DDRT with thymoglobulin induction given cPRA of 98%, with no DSA. Post-transplant allograft function was excellent with nadir creatinine of 0.8 mg/dL. Non-invasive allograft injury surveillance showed an acute rise in dd-cfDNA to 3.9% on post-operative week 5. Despite stable creatinine, a renal biopsy showed C4D-negative, mild antibody mediated rejection with peritubular capillaritis (ptc 2) and glomerulitis (g1). Antibody assessment showed no DSA but positive AT1R at 16 U/mL. Following Losartan initiation, dd-cfDNA decreased to <1%, with continued excellent graft function.
Discussion
AT1R-Ab may be more prevalent in the re-transplant population and is a causative factor for accelerated allograft injury, chronic fibrosis, and graft loss. Early detection of kidney injury via dd-cfDNA, prompt assessment of AT1R-Ab, and initiation of ARB therapy may lead to preserved allograft function, particularly in high immunologic risk patients.